The prevalence of electronic nicotine delivery system (ENDS) use among adolescents is increasing exponentially, with significant use among non-traditional cigarette (TC) smokers. It is imperative that we learn how ENDS affect adolescents because these products contain the addictive ingredient nicotine, so continued use is likely to promote dependence. Given the rapid uptake of ENDS among teens, there is a critical need to understand the safety of these products in adolescents, including 1) how use contributes to toxicant exposure and 2) identification of possible biologic mediators of usage and dependence, such as the nicotine metabolic rate. Objective: We will investigate the presence of toxicants and examine the influence of the rate of nicotine metabolism on use behaviors and nicotine dependence in adolescent ENDS-only users. Specific Aims: Investigate the level of toxicants including propylene oxide, acrolein, ethylene oxide, benzene, acrylamide, formaldehyde, and 1,3, butadiene found in adolescent ENDS-only users (AIM 1). Examine the association between the rate of nicotine metabolism measured by the salivary 3'hydroxycotinine/cotinine ratio and the frequency of ENDS use and reported dependence in adolescent ENDS-only users (AIM 2). Study Design: Using a cross-sectional design with 180 ENDS-only using adolescents (13-17 years of age) we will examine how ENDS use contributes to toxicant exposure. We will also assess whether an individual's rate of nicotine metabolism may be a biologic mediator of ENDS use and dependence. Urine samples will be analyzed for anabasine, NNAL and toxicant levels in ENDS-only users and a control group of 20 similarly aged adolescent non-smokers/non-ENDS users. ENDS behavior questionnaires and nicotine dependence scales will be administered. Saliva samples will be obtained for determination of the nicotine metabolic rate. ENDS-only usage will be verified by cotinine, and differentiated from TC exposure by the measurement of urine anabasine and NNAL. Significance: The use of ENDS has surpassed use of TC among adolescents. Because most adults addicted to TCs began during adolescence, it is essential that we understand the biological impact of ENDS use in adolescents, as we have done with TCs. The proposed study is an important step toward achieving this ultimate objective for several reasons. First, determining the in vivo toxicant load in adolescent ENDS users can provide vital prevention information for prospective users, policy makers and clinicians. Second, identifying biologic risk factors, such as the nicotine metabolic rate, that may promote heavier ENDS use and dependence is a step toward the development of successful prevention and ENDS cessation interventions in this age group. Results from this study will provide the necessary pilot data to pursue longitudinal investigations into patterns of adolescent ENDS use, toxicant exposure, and development of dependence.